Usual Adult Dose for:

Usual Pediatric Dose for:

Additional dosage information:

Usual Adult Dose for Opiate Dependence

Buprenorphine monotherapy is generally used for induction; buprenorphine/naloxone sublingual film, Bunavail(R) buccal film and Zubsolv(R) sublingual tablet may be used for induction in patients dependent on heroin or short-acting opioid products.

Bunavail(R) Buccal Film:
INDUCTION dose:
-Day 1: Initial dose: 2.1 mg/0.3 mg buccally; followed in intervals of approximately 2 hours with additional doses to a total dose of 4.2 mg/0.7 mg to control acute withdrawal symptoms
-Day 2: a single dose up to 8.4 mg/1.4 mg buccally

Zubsolv(R) Sublingual Tablets:INDUCTION dose:
-Day 1: Initial dose: 1.4 mg/0.36 mg sublingually; followed in intervals of 1.5 to 2 hours with additional doses of 1.4 mg/0.36 mg or 2.8 mg/0.72 mg to control acute withdrawal symptoms up to a total day 1 dose of 5.7 mg/1.4 mg (some patients with recent exposure to buprenorphine may tolerate up to 4.2 mg/1.08 mg as a single, second dose)
-Day 2: 11.4 mg/2.9 mg sublingually

Comments:
-To avoid precipitating withdrawal during induction, initiation should occur when clear signs of withdrawal are evident, preferably when moderate objective signs of opioid withdrawal appear, and no sooner than 6 hours after last use of heroin or other short-acting opioid.
-For patients dependent on methadone or long-acting opioid products, the presence of naloxone which may be absorbed in small amounts by the sublingual route, could precipitate or prolong withdrawal during the induction; buprenorphine monotherapy should be used during induction phase.
-Maintenance treatment begins on day 3.

MAINTENANCE Treatment:
-Doses of buprenorphine/naloxone should be adjusted to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms; doses should be titrated to clinical effectiveness as rapidly as possible as gradual titration may lead to higher drop-out rates.-The following buprenorphine/naloxone products are available for maintenance treatment; these products are not bioequivalent and dose adjustments may be necessary when switching products:

Use: For the treatment of opioid dependence as part of a complete treatment plan to include counseling and psychosocial support.

Usual Pediatric Dose for Opiate Dependence

16 years or older:
Buprenorphine monotherapy is generally used for induction; buprenorphine/naloxone sublingual film and Zubsolv(R) sublingual tablet may be used for induction in patients dependent on heroin or short-acting opioid products.

Zubsolv(R) Sublingual Tablets:INDUCTION dose:
-Day 1: Initial dose: 1.4 mg/0.36 mg sublingually; followed in intervals of 1.5 to 2 hours with additional doses of 1.4 mg/0.36 mg or 2.8 mg/0.72 mg to control acute withdrawal symptoms up to a total day 1 dose of 5.7 mg/1.4 mg (some patients with recent exposure to buprenorphine may tolerate up to 4.2 mg/1.08 mg as a single, second dose)
-Day 2: 11.4 mg/2.9 mg sublingually

Comments:
-To avoid precipitating withdrawal during induction, initiation should occur when clear signs of withdrawal are evident, preferably when moderate objective signs of opioid withdrawal appear, and no sooner than 6 hours after last use of heroin or other short-acting opioid.
-For patients dependent on methadone or long-acting opioid products, the presence of naloxone which may be absorbed in small amounts by the sublingual route, could precipitate or prolong withdrawal during the induction; buprenorphine monotherapy should be used during induction phase.
-Maintenance treatment begins on day 3.

MAINTENANCE Treatment:
-Doses of buprenorphine/naloxone should be adjusted to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms; doses should be titrated to clinical effectiveness as rapidly as possible as gradual titration may lead to higher drop-out rates.
-The following buprenorphine/naloxone products are available for maintenance treatment; these products are not bioequivalent and dose adjustments may be necessary when switching products:
SUBOXONE(R) Sublingual Film and Sublingual Tablets:
-Progressively adjust in increments/decrements of 2 mg/0.5 mg or 4 mg/1 mg to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms
-Recommended target dose: 16 mg/4 mg sublingually once a day; dose range 4 mg/1 mg to 24 mg/6 mg
-Maximum dose: 24 mg/6 mg sublingually once a day

Use: For the treatment of opioid dependence as part of a complete treatment plan to include counseling and psychosocial support.

Renal Dose Adjustments

Use with caution.

Liver Dose Adjustments

Severe Hepatic impairment: Use not recommended
Moderate Hepatic Impairment: Not recommended for induction due to increased risk of precipitated withdrawal; may be used cautiously for maintenance treatment; monitor for opioid withdrawal.
Mild hepatic impairment: Use with caution.

Dose Adjustments

Patients switching between buprenorphine-naloxone products must be monitored for over-medication or under-dosing, i.e., signs of withdrawal.

For patients switching between SUBOXONE(R) sublingual film and SUBOXONE(R) buprenorphine/naloxone sublingual tablets:
-Patients should start on the same dose as the previously administered product, however, due to greater relative bioavailability of sublingual film compared to sublingual tablet, closely monitor..

-Patients starting or ending CYP450 3A4 inhibitors or inducers should be monitored for potential over-medication or under-dosing of this drug.

REDUCING DOSAGE AND STOPPING TREATMENT:
-As part of a comprehensive treatment plan, a decision may be made to lower the maintenance dose or discontinue therapy; gradual dose reduction is recommended to avoid opioid withdrawal signs and symptoms. Following discontinuation, patients should be monitored for potential relapse.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Buprenorphine Transmucosal Products for Opioid Dependence (BTOD). It includes a medication guide, elements to assure safe use, and implementation system. For additional information: www.fda.gov/REMS

Under the Drug Addiction Treatment Act (DATA) codified at 21 U.S.C 823 (g), prescription use of this product in the treatment of opioid dependence is limited to physicians who meet certain qualifying requirements, and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription.

Safety and efficacy have not been established in patients younger than 16 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule lll

Dialysis

Data not available

Other Comments

Administration advice:
-Proper administration technique should be demonstrated to the patient
-Do not cut, chew, or swallow products
-Do not eat or drink anything until the dose is completely dissolved
-Do not move product after placement
-To ensure consistency, follow the same manner of dosing with continued use
-If a dose is missed, take it as soon as remembered; if it is almost time for the next dose, skip the missed dose and take the next dose at the regular time

-SUBLINGUAL TABLET:
-Place under tongue until dissolved
-For doses requiring multiple tablets, place all tablets in different locations under tongue, minimize overlapping; alternatively, divide into multiple portions, taking second and subsequent portions directly after previous portion has dissolved
-Median dissolution time for Zubsolv(R) was 5 minutes

SUBLINGUAL FILM:
-Before administration, drink water to moisten mouth
-Place film under tongue close to the base on the left or right side; keep under tongue until completely dissolved; on average dissolution takes 4 to 8 minutes
-For doses requiring multiple films, place additional film on the opposite side minimizing overlap as much as possible; alternatively, divide into multiple portions, taking second and subsequent portions directly after previous portion has dissolved

BUCCAL FILM:
-Use tongue to wet inside of the cheek or rinse mouth with water to moisten application area
-Apply to inside of the cheek; press and hold for 5 seconds
-Allow film to completely dissolve; avoid manipulating film with tongue or fingers
-If multiple films are needed, immediately apply the next film in the same manner to the opposite cheek; up to 2 films can be applied to one cheek at a time

Preparation techniques:
-FILM: Wait to open foil pack until ready to use; protect from freezing and moisture
-TABLET: Wait to open blister until ready for use: do not push tablet through blister pack as it may break

General:
-Treatment should be under the supervision of a physician experienced in the management of opiate dependence/addiction.
-Medication treatment should be used as part of a complete treatment plan to include counseling and psychosocial support.
-To avoid precipitating withdrawal, buprenorphine monotherapy is generally used for induction, especially when there is doubt about the level of dependence or previous drug use.
-Multiple refills should not be provided early in treatment or without appropriate follow-up.
-The decision to discontinue treatment should be made as part of a comprehensive treatment plan; abrupt discontinuation is not recommended.

Monitoring:
-Monitor for under and over dosing.
-Hepatic: Regular monitoring of liver function tests is recommended.
-If treatment goals are not being achieved, patients should be re-evaluated to determine the appropriateness of treatment or need for more intensive and structured treatment.

Patient advice:
-Advise patients to store this drug safely out of the sight and reach of children; accidental use by children is a medical emergency and can result in death.
-Advise patients that abusing this product by injecting it may cause serious withdrawal symptoms due to the presence of naloxone.
-Patients should understand the risk of life-threatening respiratory depression, and be informed as to when this risk is greatest.
-This drug may cause drowsiness, dizziness, or impair thinking, or motor skills; patients should avoid driving or operating machinery until adverse effects are determined.
-Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary.
-Patients should be instructed in proper disposal.